J Allergy Clin Immunol. 2017 Feb 7
Kreiner E, Waage J, Stand M, Brix S, Pers TH, Couto Alves A, Warrington NM, Tiesler CM, Fuertes E, Franke L, Hirschhorn JN, James A, Simpson A, Tung JY, Koppelman GH, Postma DS, Pennell CE, Jarvelin MR, Custovic A, Timpson N, Ferreira MA, Strachan DP, Henderson J, Hinds D, Bisgaard H, Bønnelykke K.
Abstract
BACKGROUND:
The relationship between allergy and autoimmune disorders is complex and poorly understood.
OBJECTIVE:
To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms.
METHODS:
We meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases.
RESULTS:
Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at a false discovery rate.
CONCLUSION:
We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared diseases mechanisms. Further studies of these shared genetic mechanisms might help understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.
KEYWORDS:
Allergy; Autoimmune Disease; Autoimmunity; Genetic Association Studies; Single Nucleotide Polymorphism
PMID: 28188724
